Article: article from journal or magazin.
Caspase-1 activity affects AIM2 speck formation/stability through a negative feedback loop.
Frontiers in Cellular and Infection Microbiology
The inflammasome is an innate immune signaling platform leading to caspase-1 activation, maturation of pro-inflammatory cytokines and cell death. Recognition of DNA within the host cytosol induces the formation of a large complex composed of the AIM2 receptor, the ASC adaptor and the caspase-1 effector. Francisella tularensis, the agent of tularemia, replicates within the host cytosol. The macrophage cytosolic surveillance system detects Francisella through the AIM2 inflammasome. Upon Francisella novicida infection, we observed a faster kinetics of AIM2 speck formation in ASC(KO) and Casp1(KO) as compared to WT macrophages. This observation was validated by a biochemical approach thus demonstrating for the first time the existence of a negative feedback loop controlled by ASC/caspase-1 that regulates AIM2 complex formation/stability. This regulatory mechanism acted before pyroptosis and required caspase-1 catalytic activity. Our data suggest that sublytic caspase-1 activity could delay the formation of stable AIM2 speck, an inflammasome complex associated with cell death.
Animals, Apoptosis Regulatory Proteins, CARD Signaling Adaptor Proteins, Caspase 1/genetics, Caspase 1/metabolism, Cell Death, Cell Line, Cytoskeletal Proteins/genetics, DNA-Binding Proteins, Feedback, Francisella tularensis/immunology, Gene Deletion, Humans, Macrophages/immunology, Macrophages/microbiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Nuclear Proteins/metabolism, AIM2, Francisella tularensis, caspase-1, inflammasome, regulation
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